Academic Unit of Surgery, School of Medicine Dentistry and Nursing, College of Medicine Veterinary and Life Sciences, University of Glasgow, Glasgow Royal Infirmary, Glasgow, UK.
Department of Experimental Therapeutics, Institute of Cancer Sciences, College of Medicine Veterinary and Life Sciences, University of Glasgow, Glasgow, UK.
J Pathol Clin Res. 2020 Jan;6(1):30-39. doi: 10.1002/cjp2.143. Epub 2019 Oct 14.
The tumour microenvironment (TME) is recognised as an important prognostic characteristic and therapeutic target in patients with colorectal cancer (CRC). However, assessment generally utilises surgically resected specimens, precluding neoadjuvant targeting. The present study investigated the feasibility of intra-epithelial CD3 T-lymphocyte density and tumour stroma percentage (TSP) assessment using preoperative colonoscopic biopsies from 115 patients who had undergone resection of stages I-III CRC, examining the relationship between biopsy and surgically resected specimen-based assessment, and the relationship with cancer-specific survival (CSS). High biopsy CD3 density was associated with high CD3 density in the invasive margin, cancer stroma and intra-epithelial compartments of surgically resected specimens (area under the curve > 0.62, p < 0.05 for all) and with high Immunoscore. High biopsy TSP predicted high TSP in resected specimens (p = 0.001). Intra-class correlation coefficient for both measures was >0.7 (p < 0.001), indicating excellent concordance between individuals. Biopsy CD3 density (hazard ratio [HR] 0.23, p = 0.002) and TSP (HR 2.23, p = 0.029) were independently associated with CSS; this was comparable to the prognostic value of full section assessment (HR 0.21, p = 0.004, and HR 2.25, p = 0.033 respectively). These results suggest that assessment of the TME is comparable in biopsy and surgically resected specimens from patients with CRC, and biopsy-based assessment could allow for stratification prior to surgery or commencement of therapy targeting the TME.
肿瘤微环境（TME）被认为是结直肠癌（CRC）患者的一个重要预后特征和治疗靶点。然而，评估通常利用手术切除的标本，排除了新辅助靶向治疗。本研究调查了使用 115 例接受 I-III 期 CRC 切除术的患者术前结肠镜活检评估上皮内 CD3 T 淋巴细胞密度和肿瘤间质百分比（TSP）的可行性，检查了活检和手术切除标本评估之间的关系，以及与癌症特异性生存（CSS）的关系。高活检 CD3 密度与手术切除标本的侵袭边缘、癌症基质和上皮内 CD3 密度高（曲线下面积>0.62，p<0.05）以及免疫评分高相关。高活检 TSP 预测切除标本中 TSP 高（p=0.001）。两种方法的组内相关系数均>0.7（p<0.001），表明个体之间具有极好的一致性。活检 CD3 密度（危险比 [HR]0.23，p=0.002）和 TSP（HR2.23，p=0.029）与 CSS 独立相关；这与全切片评估的预后价值相当（HR0.21，p=0.004，和 HR2.25，p=0.033）。这些结果表明，CRC 患者的活检和手术切除标本的 TME 评估具有可比性，基于活检的评估可以在手术前或开始针对 TME 的治疗前进行分层。
